Project Summary The goal of the present proposal is to establish and provide support for a High Spatial and Temporal Resolution Imaging Core (HSTRI or Core C) facility that will offer a wide array of state- of-the-art instruments enabling visualization of cells and tissues samples pharmacologically or genetically labeled with fluorescent indicators. With the assistance of expert staff and unrestricted access to these instruments, we expect Core C to greatly enhance the competitiveness of Project Leaders in grant applications, and promote their recognition and contributions to their respective fields at the national and international level. This facility is specifically designed to meet the needs of our Project Leaders, but will also enhance the overall capacity for biomedical research at the University of Nevada, Reno, and UNR School of Medicine. Core C will accomplish the following Specific Aims during Phase I of the COBRE: Specific Aim 1: To establish, maintain, and operate a facility providing state-of-the-art high spatial and temporal resolution imaging methodologies for studying cellular structure, signaling pathways, and function in health and disease. Recent advances in microscopy have produced a generation of commercially available instruments that provide biomedical researchers the ability to investigate the relationship between structure and function of biological systems with unprecedented spatial and temporal resolution, near or below the diffraction limit. The goal of this Specific Aim is to make high spatial and temporal resolution imaging available as a core facility to COBRE investigators. A comprehensive core management plan will be implemented to effectively maintain the infrastructure of this core and prioritize access of core services to COBRE investigators. Specific Aim 2: To advise and train investigators in the use of the new technologies. Training users in the operation of the HSTRI core equipment and appropriate sample preparation, as well as educating them about the scientific possibilities offered by these facilities, is a crucial part of maximizing the core's impact on biomedical research. Core personnel will provide appropriate training and supervision of users. Specific Aim 3: To develop a user base and an operational plan that will sustain the core in the long-term. Plans will be developed to sustain support for the Core during and after the end of the funded period through user fees. HSTRI core services will also be offered to non-COBRE investigators on a recharge basis during time slots not reserved by COBRE investigators. Many well-funded labs at UNR Med and UNR have expressed interest in incorporating high resolution imaging methods into their research and future grant applications.